Aufbau kondensierter Heterocyclen aus Anthranilsäureester und Lactonen

Abstract

Umsetzung von Anthranilsiiureester (3) mit y-Butyrolacton (4) fuhrt bei 270°C im Druckrohr zur pentacyclischen Verbindung 2, deren Struktur durch eine unabhangige Synthese gesichert wird. Die Anwendung der Reaktion auf andere Lactone (12, 15) wird untersucht ( > 13, 16). Synthesis of Condensed Heterocycles from Anthranilic Ester and LactonesAnthranilic ester (3) reacts with y-butyrolactone (4) at 270°C in a sealed tube to give the pentacyclic compound 2, the structure of which is confirmed by synthesis from unequivocally prepared intermediates. The application of the reaction to other lactones (12, 15) is studied (+13,16).Astill und Boekelheide 1) berichteten im Rahmen der Synthese von 1-Benzazepin-Derivaten iiber erfolglose Versuche mit der Sputhschen Methode *), in Anthranilsaure oder Ant hranilsgure-methylester (3) niit y-Butyrolacton (4) eine Methoxycarbonylpropyl-Gruppe einzufuhren. Es kam dabei zur Eliminierung der Carboxyloder Methoxycarbonyl-Gruppe unter Bildung von I-Phenyl-2-pyrrolidon bzw. Anilin. A h Nebenprodukt erhielten sie in geringer Ausbeute eine gelbe Suhstanz, die sie allein durch die Elementaranalyse charakterisierten, fur die aber kein Strukturvorschlag gemacht werden konnte.Wir bearbeiteten im Zusammenhang mit einer anderen Fragestellung diese Reaktion und klarten die Struktur der gelben Substam auf. Eine kurzlich erschienene Arbeit von McCall, Proctor und Purdie3) veranlaRt uns, die bisherigen Ergehnisse mitzuteilen. Die englischen Autoren untersuchten dieReaktion von 3 mit4-Brombuttersauremethylester und erhielten in minimaler Ausbeute eine gelbe Substanz, von der sie ohne Beweise in einer Funnote erwahnen, daR ,,sie mit dem Produkt von Astill und Boekelheide identisch zu sein scheine'&.

Rapid Access to a Pentacyclic Library Core Structure: A Microwave Assisted Approach

“…Due to restrictions imposed by the equipment, we were only able to carry out this reaction on 1/25 th of the scale reported for the sealed vessel reaction in the literature [3]. Whilst a significant reduction in the reaction times was possible (30 minutes vs 4 hours) we were unable to improve the yield for this transformation (7% vs 21.5% based on 5).…”

“…Whilst a significant reduction in the reaction times was possible (30 minutes vs 4 hours) we were unable to improve the yield for this transformation (7% vs 21.5% based on 5). 3 ) and TLC analysis of the filtrate showed that a small amount of 4 was present. The relative insolubility of 4 and the complex mixture of products hampered isolation of this additional amount of sample.…”

“…In this study, we report our attempts to prepare 4 using microwave techniques. We also describe a microwave-based approach to analogues of 4 that have differentially substituted aryl rings (A and E, Scheme 3) and/or additional atoms in ring C. Finally we describe an alternative approach to 4 that provides experimental support for a possible mechanism for the reported one-pot transformation [3].…”

“…A literature search of compounds related to quinolone 3, a key intermediate in an alternative approach to 1, led us to the reported synthesis of 8,14-dioxo-6,7-dihydro-8H,14H-5,13-diazabenz[e]aceanthrylene (4) (Scheme 2). Pentacycle 4 was previously prepared in a single step by heating methyl anthranilate (5) and g-butyrolactone (6) in a sealed vessel at 270 8C [3]. Due to the relative insolubility of 4 in organic solvents, it was reported that 4 could be obtained in 21.5% yield (based on 5) following precipitation, filtration and recrystallisation.…”

One-Pot Synthesis of Simple Alkaloids: 2,3-Polymethylene-4(3<i>H</i>)-quinazolinones, Luotonin A, Tryptanthrin, and Rutaecarpine

“…1,[30][31][32][33] Although most of these are applicable to acyclic amides, methods for cyclic amides, especially without an aryl group, are somewhat limited. [34][35][36][37] These limitations have led to the continuous development of new procedures for cyclic amides, such as cyclocondensation of isatoic anhydride with lactams, 12) metal catalyzed reductive N-heterocyclization of N- (2-nitrobenzoyl)lactams in the presence of CO, 13,14) reaction of 2-aminobenzamide with succinic anhydride, 15) intramolecular aza-Wittig reaction of N-(2-azidobenzoyl)lactams, 9,16) condensation of anthranilic acid with O-alkyllactims 6,[18][19][20] or S-alkyllactims, 8) reaction of anthranilic acid with SOCl 2 followed by cyclization with lactams, 17) cyclization of iminochlorides generated from lactam and methyl anthranilate, 11) solid-phase synthesis, 7,9) and microwave assisted synthesis.…”